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ADVATE® [Antihemophilic Factor (Recombinant)] Important Information

What is ADVATE?

ADVATE is a medicine used to replace clotting factor (factor VIII or antihemophilic factor) that is missing in people with hemophilia A (also called “classic” hemophilia).

ADVATE is used to prevent and control bleeding in adults and children (0-16 years) with hemophilia A. Your healthcare provider (HCP) may give you ADVATE when you have surgery.

ADVATE can reduce the number of bleeding episodes in adults and children (0-16 years) when used regularly (prophylaxis).

ADVATE is not used to treat von Willebrand disease.

DETAILED IMPORTANT RISK INFORMATION

Who should not use ADVATE?

Do not use ADVATE if you:

Are allergic to mice or hamsters.

Are allergic to any ingredients in ADVATE.

Tell your HCP if you are pregnant or breastfeeding because ADVATE may not be right for you.

What should I tell my HCP before using ADVATE?

Tell your HCP if you:

Have or have had any medical problems.

Take any medicines, including prescription and non-prescription medicines, such as over-the-counter medicines, supplements or herbal remedies.

Have any allergies, including allergies to mice or hamsters.

Are breastfeeding. It is not known if ADVATE passes into your milk and if it can harm your baby.

Are or become pregnant. It is not known if ADVATE may harm your unborn baby.

Have been told that you have inhibitors to factor VIII (because ADVATE may not work for you).

What important information do I need to know about ADVATE?

You can have an allergic reaction to ADVATE. Call your HCP right away and stop treatment if you get a rash or hives, itching, tightness of the throat, chest pain or tightness, difficulty breathing, lightheadedness, dizziness, nausea or fainting.

Do not attempt to infuse yourself with ADVATE unless you have been taught by your HCP or hemophilia center.

What else should I know about ADVATE and Hemophilia A?

Your body may form inhibitors to factor VIII. An inhibitor is part of the body’s normal defense system. If you form inhibitors, it may stop ADVATE from working properly. Talk with your HCP to make sure you are carefully monitored with blood tests for the development of inhibitors to factor VIII.

What are possible side effects of ADVATE?

Side effects that have been reported with ADVATE include: cough, headache, joint swelling/aching, sore throat, fever, itching, unusual taste, dizziness, hematoma, abdominal pain, hot flashes, swelling of legs, diarrhea, chills, runny nose/congestion, nausea/vomiting, sweating, and rash. Tell your HCP about any side effects that bother you or do not go away or if your bleeding does not stop after taking ADVATE.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

ADYNOVATE is an injectable medicine that is used to help treat and control bleeding in children and adults with hemophilia A (congenital Factor VIII deficiency).

Your healthcare provider (HCP) may give you ADYNOVATE when you have surgery.

ADYNOVATE can reduce the number of bleeding episodes when used regularly (prophylaxis).

ADYNOVATE is not used to treat von Willebrand disease.

DETAILED IMPORTANT RISK INFORMATION

Who should not use ADYNOVATE?

Do not use ADYNOVATE if you:

Are allergic to mice or hamster protein

Are allergic to any ingredients in ADYNOVATE or ADVATE [Antihemophilic Factor (Recombinant)]

Tell your HCP if you are pregnant or breastfeeding because ADYNOVATE may not be right for you.

What should I tell my HCP before using ADYNOVATE?

Tell your HCP if you:

Have or have had any medical problems.

Take any medicines, including prescription and non-prescription medicines, such as over-the-counter medicines, supplements or herbal remedies.

Have any allergies, including allergies to mice or hamsters.

Are breastfeeding. It is not known if ADYNOVATE passes into your milk and if it can harm your baby.

Are or become pregnant. It is not known if ADYNOVATE may harm your unborn baby.

Have been told that you have inhibitors to factor VIII (because ADYNOVATE may not work for you).

What important information do I need to know about ADYNOVATE?

You can have an allergic reaction to ADYNOVATE. Call your healthcare provider right away and stop treatment if you get a rash or hives, itching, tightness of the throat, chest pain or tightness, difficulty breathing, lightheadedness, dizziness, nausea or fainting.

Do not attempt to infuse yourself with ADYNOVATE unless you have been taught by your HCP or hemophilia center.

What else should I know about ADYNOVATE and Hemophilia A?

Your body may form inhibitors to factor VIII. An inhibitor is part of the body’s normal defense system. If you form inhibitors, it may stop ADYNOVATE from working properly. Talk with your HCP to make sure you are carefully monitored with blood tests for the development of inhibitors to factor VIII.

What are possible side effects of ADYNOVATE?

The common side effects of ADYNOVATE are headache and nausea. These are not all the possible side effects with ADYNOVATE. Tell your HCP about any side effects that bother you or do not go away.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Indications for FEIBA

FEIBA is an Anti-Inhibitor Coagulant Complex approved for use in hemophilia A and B patients with inhibitors for:

Control and prevention of bleeding episodes

Use around the time of surgery

Routine prophylaxis to prevent or reduce the frequency of bleeding episodes.

FEIBA is NOT for use in the treatment of bleeding episodes resulting from coagulation factor deficiencies without inhibitors to factor VIII or factor IX.

Detailed Important Risk Information for FEIBA

WARNING: EVENTS INVOLVING CLOTS THAT BLOCK BLOOD VESSELS

Blood clots that block blood vessels and their effects have been reported during post-marketing surveillance following infusion of FEIBA, particularly following administration of high doses (above 200 units per kg per day) and/or in patients at risk for forming blood clots.

If you experience any of these side effects, call your doctor right away.

Who should not use FEIBA?

You should not use FEIBA if:

You had a previous severe allergic reaction to the product

You have Disseminated Intravascular Coagulation (DIC), or signs of small blood vessel clots throughout the body

Events involving blood clots blocking blood vessels (such as blood clot in vein, blood clot in the lung, heart attack, and stroke) can occur with FEIBA, particularly after receiving high doses (above 200 units per kg per day) and/or in patients with risk factors for clotting.

Events of thrombotic microangiopathy (TMA), a condition where blood clots and damage occur in small blood vessels, were reported in an emicizumab (Hemlibra®) clinical trial where patients received FEIBA with emicizumab as part of a treatment plan for breakthrough bleeding. The safety and efficacy of FEIBA for breakthrough bleeding in patients receiving emicizumab has not been established. If you take, or anticipate taking, FEIBA with emicizumab, tell your doctor, since they will need to closely monitor you.

Infusion of FEIBA should not exceed a single dose of 100 units per kg body weight and daily doses of 200 units per kg of body weight. Maximum injection or infusion rate must not exceed 2 units per kg of body weight per minute.

Allergic reactions, including severe, sometimes fatal allergic reactions that can involve the whole body, can occur following the infusion of FEIBA. Stop using FEIBA promptly and call your doctor or get emergency treatment right away if you get a rash, hives or welts, experience itching, tightness of the throat, vomiting, abdominal pain, chest pain or tightness, difficulty breathing, lightheadedness, dizziness, nausea or fainting.

Because FEIBA is made from human plasma it may carry a risk of transmitting infectious agents, such as viruses, variant Creutzfeldt-Jakob disease (vCJD) and, theoretically, the Creutzfeldt-Jakob disease (CJD).

What are the possible side effects of FEIBA?

The most common side effects observed during the prophylaxis clinical study were low number of red blood cells, diarrhea, bleeding into a joint, positive test for hepatitis B surface antibodies, nausea, and vomiting.

The serious side effects seen with FEIBA are allergic reactions and clotting events involving blockage of blood vessels, which include stroke, blockage of the main blood vessel to the lung, and deep vein blood clots.

Call your doctor right away about any side effects that bother you during or after you stop taking FEIBA.

What other medications might interact with FEIBA?

Talk with your doctor about the possibility of formation of blood clots when taking drugs that may prevent clot breakdown such as tranexamic acid, and aminocaproic acid. There have not been adequate studies of the use of FEIBA and rFVIIa (NovoSeven®), or emicizumab together, or one after the other. Use of drugs that may prevent clot breakdown within approximately 6 to 12 hours after the administration of FEIBA is not recommended.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please see FEIBA full Prescribing Information, including BOXED WARNING on blood clots, and discuss with your doctor.

INDICATIONS

HEMOFIL M is indicated in hemophilia A (classical hemophilia) for the prevention and control of hemorrhagic episodes.

HEMOFIL M is not indicated in von Willebrand’s disease.

DETAILED IMPORTANT RISK INFORMATION

You should not use HEMOFIL M if you are allergic to mouse proteins or any ingredients in HEMOFIL M.

Allergic reactions, including anaphylaxis, have been reported with HEMOFIL M. The symptoms of an allergic reaction may include anaphylaxis, wheezing, difficulty breathing, low blood pressure, lightheadedness, dizziness, fainting, chest tightness or pain, facial swelling, hives, rash, flushing, itching or nausea. If you experience any of these symptoms, discontinue use of the product and contact your healthcare provider right away.

Inhibitors to Factor VIII have been reported with the use of HEMOFIL M. Your body may form inhibitors to Factor VIII. Inhibitors are part of your body’s normal defense system. If you form inhibitors, it may stop HEMOFIL M from working properly. Consult with your healthcare provider to make sure you are carefully monitored with blood tests for development of inhibitors to Factor VIII.

Because HEMOFIL M is made from human blood, it may carry a risk of transmitting infectious agents, e.g., viruses such as parvovirus B19 or hepatitis A, the variant Creutzfeldt-Jakob disease (vCJD) agent and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. This also applies to unknown or emerging viruses and other pathogens. Parvovirus B19 infection is especially serious in pregnant women or immune-compromised individuals. Symptoms of parvovirus B19 infection include fever, drowsiness, chills, and runny nose followed about two weeks later by a rash and joint pain. Symptoms of hepatitis A may include several days to weeks of poor appetite, tiredness, and low-grade fever followed by nausea, vomiting, and pain in the belly. Dark urine and a yellowed complexion are also common symptoms. Discontinue use of the product and contact your healthcare provider right away if such symptoms occur. All infections thought by your doctor possibly to have been transmitted by this product should be reported by the doctor or other healthcare provider to Shire Drug Safety (Baxalta related products) at 1-800-999-1785.

HEMOFIL M is for treating patients with Factor VIII deficiency (hemophilia A), and it is essential that you are diagnosed before using HEMOFIL M.

You should tell your doctor if you have had any medical problems, take any medicines, including prescription and non-prescription medicines and dietary supplements, have any allergies including allergies to mouse proteins, are nursing, are pregnant or have been told that you have inhibitors to Factor VIII.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

INDICATIONS

RECOMBINATE™ [Antihemophilic Factor (Recombinant)] is indicated in hemophilia A (classical hemophilia) for the prevention and control of hemorrhagic episodes and for the perioperative management of patients with hemophilia A.

RECOMBINATE is not indicated for von Willebrand’s disease.

DETAILED IMPORTANT RISK INFORMATION

You should not use RECOMBINATE if you are allergic to mouse, hamster, or bovine proteins or if you are allergic to any ingredients in RECOMBINATE.

RECOMBINATE is for treating patients with Factor VIII deficiency (hemophilia A), and it is essential that you are diagnosed before using RECOMBINATE.

You should tell your doctor if you have or have had any medical problems; take any medicines, including prescription and non-prescription medicines, dietary supplements and herbal remedies; have any allergies, including allergies to mouse, hamster, or bovine proteins; are nursing; are pregnant; or have been told that you have inhibitors to Factor VIII (because Factor VIII may not work for you).

You could have an allergic reaction to RECOMBINATE. Symptoms of an allergic reaction may include rash or hives, itching, tightness of the throat, chest pain or tightness, difficulty breathing, lightheadedness, dizziness, or fainting. If you have an allergic reaction, call your doctor right away and stop treatment.

Your body may form inhibitors to Factor VIII. Inhibitors are part of your body’s normal defense system. If you form inhibitors, it may stop RECOMBINATE from working properly. Consult with your doctor to make sure you are carefully monitored with blood tests for the development of inhibitors to Factor VIII.

The most common side effects are chills, flushing, rash, and nose bleed.

Call your doctor right away about any side effects that bother you or if your bleeding does not stop after taking RECOMBINATE.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

RIXUBIS® [COAGULATION FACTOR IX (RECOMBINANT)] Important Information

INDICATIONS

RIXUBIS is an injectable medicine used to replace clotting factor IX that is missing in adults and children with hemophilia B (also called congenital factor IX deficiency or Christmas disease).

RIXUBIS is used to control and prevent bleeding in people with hemophilia B. Your healthcare provider may give you RIXUBIS when you have surgery. RIXUBIS can reduce the number of bleeding episodes when used regularly (prophylaxis).

DETAILED IMPORTANT RISK INFORMATION

You should not use RIXUBIS if you are allergic to hamsters or any ingredients in RIXUBIS.

You should tell your healthcare provider if you have or have had any medical problems, take any medicines, including prescription and non-prescription medicines, such as over-the-counter medicines, supplements or herbal remedies, have any allergies, including allergies to hamsters, are nursing, are pregnant or planning to become pregnant, or have been told that you have inhibitors to factor IX.

Allergic reactions have been reported with RIXUBIS. Call your healthcare provider or get emergency treatment right away if you get a rash or hives, itching, tightness of the throat, chest pain or tightness, difficulty breathing, lightheadedness, dizziness, nausea, or fainting.

Your body may form inhibitors to factor IX. An inhibitor is part of the body’s defense system. If you form inhibitors, it may stop RIXUBIS from working properly. Consult with your healthcare provider to make sure you are carefully monitored with blood tests for development of inhibitors to factor IX.

If you have risk factors for developing blood clots, the use of factor IX products may increase the risk of abnormal blood clots.

Common side effects that have been reported with RIXUBIS include: unusual taste in the mouth, limb pain, and atypical blood test results.

Call your healthcare provider right away about any side effects that bother you or if your bleeding does not stop after taking RIXUBIS.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

VONVENDI® [von Willebrand factor (recombinant)] Important Information

What is VONVENDI?

VONVENDI is used in adults (age 18 years and older) diagnosed with von Willebrand disease to:

treat and control bleeding episodes

prevent excessive bleeding during and after surgery

Detailed Important Risk Information

Who should not use VONVENDI?

You should not use VONVENDI if you:

Are allergic to any ingredients in VONVENDI.

Are allergic to mice or hamsters.

Tell your healthcare provider if you are pregnant or breastfeeding because VONVENDI may not be right for you.

How should I use VONVENDI?

Your first dose of VONVENDI for each bleeding episode may be administered with a recombinant factor VIII as instructed by your healthcare provider.

Your healthcare provider will instruct you whether additional doses of VONVENDI with or without recombinant factor VIII are needed.

What should I tell my healthcare provider before I use VONVENDI?

You should tell your healthcare provider if you:

Have or have had any medical problems.

Take any medicines, including prescription and non-prescription medicines, such as over-the-counter medicines, supplements or herbal remedies.

Have any allergies, including allergies to mice or hamsters.

Are breastfeeding. It is not known if VONVENDI passes into your milk and if it can harm your baby.

Are pregnant or planning to become pregnant. It is not known if VONVENDI can harm your unborn baby.

Have been told that you have inhibitors to von Willebrand factor (because VONVENDI may not work for you).

Have been told that you have inhibitors to blood coagulation factor VIII.

What else should I know about VONVENDI and von Willebrand Disease?

Your body can form inhibitors to von Willebrand factor or factor VIII. An inhibitor is part of the body's normal defense system. If you form inhibitors, it may stop VONVENDI or factor VIII from working properly. Consult with your healthcare provider to make sure you are carefully monitored with blood tests for the development of inhibitors to von Willebrand factor or factor VIII.

What are the possible side effects of VONVENDI?

You can have an allergic reaction to VONVENDI.

Call your healthcare provider right away and stop treatment if you get a rash or hives, itching, tightness of the throat, chest pain or tightness, difficulty breathing, lightheadedness, dizziness, nausea or fainting.